The intestinal microbiota regulates host cholesterol homeostasis
Abstract Background Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale. Results We depleted the intestinal microbiota of hyper...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-11-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12915-019-0715-8 |
| _version_ | 1818154039760650240 |
|---|---|
| author | Tiphaine Le Roy Emelyne Lécuyer Benoit Chassaing Moez Rhimi Marie Lhomme Samira Boudebbouze Farid Ichou Júlia Haro Barceló Thierry Huby Maryse Guerin Philippe Giral Emmanuelle Maguin Nathalie Kapel Philippe Gérard Karine Clément Philippe Lesnik |
| author_facet | Tiphaine Le Roy Emelyne Lécuyer Benoit Chassaing Moez Rhimi Marie Lhomme Samira Boudebbouze Farid Ichou Júlia Haro Barceló Thierry Huby Maryse Guerin Philippe Giral Emmanuelle Maguin Nathalie Kapel Philippe Gérard Karine Clément Philippe Lesnik |
| author_sort | Tiphaine Le Roy |
| collection | DOAJ |
| description | Abstract Background Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale. Results We depleted the intestinal microbiota of hypercholesterolemic female Apoe −/− mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa. Conclusions These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases. |
| first_indexed | 2024-12-11T14:20:10Z |
| format | Article |
| id | doaj.art-ec015530eaa94243bf60ad1b8a5d545c |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-11T14:20:10Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-ec015530eaa94243bf60ad1b8a5d545c2022-12-22T01:02:57ZengBMCBMC Biology1741-70072019-11-0117111810.1186/s12915-019-0715-8The intestinal microbiota regulates host cholesterol homeostasisTiphaine Le Roy0Emelyne Lécuyer1Benoit Chassaing2Moez Rhimi3Marie Lhomme4Samira Boudebbouze5Farid Ichou6Júlia Haro Barceló7Thierry Huby8Maryse Guerin9Philippe Giral10Emmanuelle Maguin11Nathalie Kapel12Philippe Gérard13Karine Clément14Philippe Lesnik15INSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreINSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreNeuroscience Institute and Institute for Biomedical Sciences, Georgia State UniversityInstitut Micalis, INRA, AgroParisTech, Université Paris-SaclayInstitute of Cardiometabolism and Nutrition (ICAN), Hôpital Pitié-SalpêtrièreInstitut Micalis, INRA, AgroParisTech, Université Paris-SaclayInstitute of Cardiometabolism and Nutrition (ICAN), Hôpital Pitié-SalpêtrièreINSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreINSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreINSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreINSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreInstitut Micalis, INRA, AgroParisTech, Université Paris-SaclayLaboratoire de Coprologie Fonctionnelle, Hôpital Pitié-SalpêtrièreInstitut Micalis, INRA, AgroParisTech, Université Paris-SaclaySorbonne/INSERM, UMRS 1269, Nutrition et obésités : approches systémiques (nutriOmics), Hôpital Pitié-SalpêtrièreINSERM, UMRS 1166, team “Integrative Biology of Atherosclerosis”, Sorbonne Universités, Hôpital Pitié-SalpêtrièreAbstract Background Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale. Results We depleted the intestinal microbiota of hypercholesterolemic female Apoe −/− mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa. Conclusions These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.http://link.springer.com/article/10.1186/s12915-019-0715-8Intestinal microbiotaMicrobiomeMicrobiota transferCholesterol metabolismEnterohepatic cycleAntibiotics |
| spellingShingle | Tiphaine Le Roy Emelyne Lécuyer Benoit Chassaing Moez Rhimi Marie Lhomme Samira Boudebbouze Farid Ichou Júlia Haro Barceló Thierry Huby Maryse Guerin Philippe Giral Emmanuelle Maguin Nathalie Kapel Philippe Gérard Karine Clément Philippe Lesnik The intestinal microbiota regulates host cholesterol homeostasis BMC Biology Intestinal microbiota Microbiome Microbiota transfer Cholesterol metabolism Enterohepatic cycle Antibiotics |
| title | The intestinal microbiota regulates host cholesterol homeostasis |
| title_full | The intestinal microbiota regulates host cholesterol homeostasis |
| title_fullStr | The intestinal microbiota regulates host cholesterol homeostasis |
| title_full_unstemmed | The intestinal microbiota regulates host cholesterol homeostasis |
| title_short | The intestinal microbiota regulates host cholesterol homeostasis |
| title_sort | intestinal microbiota regulates host cholesterol homeostasis |
| topic | Intestinal microbiota Microbiome Microbiota transfer Cholesterol metabolism Enterohepatic cycle Antibiotics |
| url | http://link.springer.com/article/10.1186/s12915-019-0715-8 |
| work_keys_str_mv | AT tiphaineleroy theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT emelynelecuyer theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT benoitchassaing theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT moezrhimi theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT marielhomme theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT samiraboudebbouze theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT faridichou theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT juliaharobarcelo theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT thierryhuby theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT maryseguerin theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT philippegiral theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT emmanuellemaguin theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT nathaliekapel theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT philippegerard theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT karineclement theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT philippelesnik theintestinalmicrobiotaregulateshostcholesterolhomeostasis AT tiphaineleroy intestinalmicrobiotaregulateshostcholesterolhomeostasis AT emelynelecuyer intestinalmicrobiotaregulateshostcholesterolhomeostasis AT benoitchassaing intestinalmicrobiotaregulateshostcholesterolhomeostasis AT moezrhimi intestinalmicrobiotaregulateshostcholesterolhomeostasis AT marielhomme intestinalmicrobiotaregulateshostcholesterolhomeostasis AT samiraboudebbouze intestinalmicrobiotaregulateshostcholesterolhomeostasis AT faridichou intestinalmicrobiotaregulateshostcholesterolhomeostasis AT juliaharobarcelo intestinalmicrobiotaregulateshostcholesterolhomeostasis AT thierryhuby intestinalmicrobiotaregulateshostcholesterolhomeostasis AT maryseguerin intestinalmicrobiotaregulateshostcholesterolhomeostasis AT philippegiral intestinalmicrobiotaregulateshostcholesterolhomeostasis AT emmanuellemaguin intestinalmicrobiotaregulateshostcholesterolhomeostasis AT nathaliekapel intestinalmicrobiotaregulateshostcholesterolhomeostasis AT philippegerard intestinalmicrobiotaregulateshostcholesterolhomeostasis AT karineclement intestinalmicrobiotaregulateshostcholesterolhomeostasis AT philippelesnik intestinalmicrobiotaregulateshostcholesterolhomeostasis |